The overall objective of our research is to understand the mechanisms involved in the regulation of mRNA metabolism in eukaryotes. We have been concentrating on the chick oviduct system where steroid hormones are involved in the regulation of egg white protein mRNA synthesis and degradation. We have developed an in vitro culture system that responds to steroids (estrogen, progesterone and glucocorticoids) in a manner that is quantitatively and qualitatively similar to the intact animal. This system will be used to study the nuclear events that lead to the activation of transcription of ovalbumin and conalbumin mRNA. More recently we have begun studying the regulation of metallothionein mRNA production in mouse liver. This small protein is induced in the liver in response to glucocorticoids and heavy metals. We have cloned this gene and intend to use it to study the regulation of metallothionein mRNA synthesis and degradation in cultured liver cells. The long range goal is to establish a cell-free transcription system that responds to steroid hormones.